Investigators evaluated 4903 patients with HCC treated with sorafenib at 128 Veterans Health Administration hospitals from January 2006 to April 2015. Patients were assigned to a standard starting dose of 800 mg daily (n = 3094) or a reduced dose of <800 mg of daily sorafenib (n = 1809).

After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HR) were calculated using Cox regression and tested against a noninferiority margin of HR equal to 1.1. Investigators performed a matched multivariate logistic regression to adjust for potential confounders.

However, after propensity score-matching and adjusting for potential confounders, the difference in OS was no longer significant (HR, 0.92; 95% CI, 0.83-1.01). Investigators said the difference was well within the noninferiority margin (P <.001).

“Ultimately, we did not find evidence that starting patients with HCC on a [reduced starting dose of sorafenib] led to a significant difference in OS, and the 95% CI included an HR of 1.0 across all examined subgroups,” first author Kim A. Reiss, MD, Perelman Center for Advanced Medicine, and co-investigators wrote. “Our data suggest that the initiation of sorafenib at a reduced dosage may be a safe and reasonable strategy for some patients with HCC.”

The median patient age was 62 years, and the cohort was overwhelmingly male (98.9%) and white (61.2%). The majority of patients (58%) had CTP class A disease, 37% had class B, and 4% had class C. Six in 10 patients had been diagnosed with either active hepatitis B or C, 43% had BCLC stage A or B HCC, 46% had BCLC stage C, and 8% had BCLC stage D.

Among standard-dose patients, 68 (2.2%) required dosage reduction within the first month, and 360 (11.6%) within the first 2 months. In contrast, 211 patients (11.7%) in the reduced-dose group needed escalation within the first month, and 539 (29.8%) within the first 2 months. After 2 months, 31.7% of reduced-dose and 33.7% of standard-dose patients had stopped sorafenib for any reason.

Reduce-dose and standard-dose patients had similar rates of discontinuation due to an adverse event (AE; 20% v 21%; P = .18), and were equally likely to remain on treatment until disease progression (27% v 28%; P = .26). Gastrointestinal toxicity was the most common reason for treatment discontinuation (456 patients), followed by fatigue (265 patients) and hand-foot skin reaction (205 patients). Patients in the reduced-dose group were significantly less likely to discontinue sorafenib for a hand-foot skin reaction (5% vs 3%; P = .05), and less likely to discontinue because of gastrointestinal AEs (8.7% vs 10.8%; P = .047).

Patients in both groups received a median of 90 days of sorafenib treatment (P <.20). However, because reduced-dose patients received less sorafenib per day, they were prescribed far fewer pills (180 vs 276; P <.001). As a result, total pill-related costs were also significantly lower for reduced-dose patients ($5636 vs 8661; P <.001).

“After propensity score matching, [reduced-dose sorafenib] patients were less likely to discontinue sorafenib because of gastrointestinal toxicity, and there were trends toward a decreased risk of discontinuing the drug for any AE,” wrote Reiss et al. [Reduced-dose sorafenib] patients experienced decreased treatment cost and a trend toward a decreased incidence of discontinuing sorafenib because of AEs.”